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The novel recreational drug 34-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats

机译:新型休闲药物34-亚甲基二氧基吡咯烷酮(MDPV)是一种强力的精神运动兴奋剂:大鼠的自我给药和运动能力

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摘要

Recreational use of the cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV; “bath salts”) has increased worldwide in past years, accompanied by accounts of health and legal problems in the popular media and efforts to criminalize possession in numerous jurisdictions. Minimal information exists on the effects of MDPV in laboratory models. This study determined the effects of MDPV, alongside those of the better studied stimulant d-methamphetamine (METH), using rodent models of intravenous self-administration (IVSA), thermoregulation and locomotor activity. Male Wistar rats were trained to self-administer MDPV or METH (0.05 mg/kg/infusion, i.v.) or were prepared with radiotelemetry implants for the assessment of body temperature and activity responses to MDPV or METH (0–5.6 mg/kg s.c.). METH and MDPV were consistently self-administered within 10 training sessions (mg/kg/hour; METH Mean=0.4 and Max = 1.15; MDPV Mean=0.9 and Max = 5.8). Dose-substitution studies demonstrated that behavior was sensitive to dose for both drugs, but MDPV (0.01–0.50 mg/kg/inf) showed greater potency and efficacy than METH (0.1–0.25 mg/kg/inf). In addition, both MDPV and METH increased locomotor activity at lower doses (0.5–1.0 mg/kg, s.c.) and transiently decreased activity at the highest dose (5.6 mg/kg, s.c.). Body temperature increased monotonically with increasing doses of METH but MDPV had a negligible effect on temperature. Stereotypy was associated with relatively high self-administered cumulative doses of MDPV (~1.5 mg/kg/hr) as well as with non-contingent MDPV administration wherein the intensity and duration of stereotypy increased as MDPV dose increased. Thus, MDPV poses a substantial threat for compulsive use that is potentially greater than that for METH.
机译:近年来,在全世界范围内娱乐性使用卡西酮衍生物3,4-亚甲基二氧基吡咯烷酮(MDPV;“沐浴盐”),伴随着大众媒体对健康和法律问题的关注,以及在许多司法管辖区将拥有财产定为犯罪的努力。关于MDPV在实验室模型中的作用的信息很少。这项研究使用啮齿动物模型的静脉内自我给药(IVSA),体温调节和运动活性,确定了MDPV的作用以及更好研究的兴奋剂d-甲基苯丙胺(METH)的作用。对Wistar雄性大鼠进行自我给药MDPV或METH(0.05 mg / kg /滴注,静脉注射)的训练,或用放射遥测植入物制备,以评估体温和对MDPV或METH的活性反应(0-5.6 mg / kg sc)。 。 METH和MDPV在10个培训课程中始终自我管理(mg / kg /小时; METH平均值= 0.4,最大值= 1.15; MDPV平均值= 0.9,最大值= 5.8)。剂量替代研究表明,两种药物的行为均对剂量敏感,但MDPV(0.01–0.50 mg / kg / inf)的药效和功效高于METH(0.1–0.25 mg / kg / inf)。此外,MDPV和METH在较低剂量(0.5–1.0 mg / kg,s.c.)下均可增加运动活性,而在最高剂量(5.6 mg / kg,s.c.)下可暂时降低运动活性。随着METH剂量的增加,体温单调增加,但MDPV对温度的影响可忽略不计。刻板印象与相对较高的MDPV自我累积剂量(〜1.5 mg / kg / hr)以及非暂时性MDPV给药有关,其中刻板印象的强度和持续时间随MDPV剂量的增加而增加。因此,MDPV对强制性使用构成了实质性威胁,其潜在危害可能大于对甲基苯丙胺的威胁。

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